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Glycine
| Section2 = | Section3 = }} Glycine (abbreviated as Gly or G) is the organic compound with the formula NH2CH2COOH. It is a non-essential [[amino acid that is an inhibitory neurotransmitterin the spinal cord, binding to receptor sites on alpha motor neurons It is the smallest of the 20 amino acids commonly found in proteins, coded by codons GGU, GGC, GGA and GGG. Glycine is unique among the proteinogenic amino acids in that it is not chiral. Most proteins contain only small quantities of glycine. A notable exception is collagen, which contains about 35% glycine.Nelson, D. L. & Cox, M. M. (2005). Lehninger Principles of Biochemistry, 4th Edition. New York: W. H. Freeman and Company, p. 127. ISBN 0-7167-4339-6. In its solid, i.e., crystallized, form, glycine is a free-flowing, sweet-tasting crystalline material. Etymology Glycine comes from the Greek glykys (sweet) +''ine'' (indicating an organi compound) Biosynthesis Glycine is not essential to the human diet, since it is biosynthesized in the body from the amino acid serine, which is in turn derived from 3-phosphoglycerate. In most organisms, the enzyme Serine hydroxymethyltransferase catalyses this transformation by removing one carbon atom; pyridoxal phosphate is also necessary:Nelson, D. L. & Cox, M. M. (2005). Lehninger Principles of Biochemistry, 4th Edition. New York: W. H. Freeman and Company, p. 844. ISBN 0-7167-4339-6. : Serine + tetrahydrofolate → Glycine + N5,N10-Methylene tetrahydrofolate + H2O In the liver of vertebrates, glycine synthesis is catalyzed by glycine synthase (also called glycine cleavage enzyme). This conversion is readily reversible: : CO2 + NH4+ + N5,N10-Methylene tetrahydrofolate + NADH + H+ → Glycine + tetrahydrofolate + NAD+ Degradation Glycine is degraded via three pathways. The predominant pathway in animals involves the catalysis of glycine cleavage enzyme, the same enzyme also involved in the biosynthesis of glycine. The degradation pathway is the reverse of this synthetic pathway:Nelson, D. L. & Cox, M. M. (2005). Lehninger Principles of Biochemistry, 4th Edition. New York: W. H. Freeman and Company, pp. 675-677. ISBN 0-7167-4339-6. : Glycine + tetrahydrofolate + NAD+ → CO2 + NH4+ + N5,N10-Methylene tetrahydrofolate + NADH + H+ In the second pathway, glycine is degraded in two steps. The first step is the reverse of glycine biosynthesis from serine with serine hydroxymethyl transferase. Serine is then converted to pyruvate by serine dehydratase. In the third pathway of glycine degradation, glycine is converted to glyoxylate by D-amino acid oxidase. Glycoxylate is then oxidized by hepatic lactate dehydrogenase to oxalate in an NAD+-dependent reaction. Physiological function As a biosynthetic intermediate Glycine is a building block to numerous natural products. In higher eukaryotes, D-Aminolevulinic acid, the key precursor to porphyrins, is biosynthesized from glycine and succinyl-CoA. Glycine provides the central C2N subunit of all purines.Nelson, D. L. & Cox, M. M. (2005). Lehninger Principles of Biochemistry, 4th Edition. New York: W. H. Freeman and Company, p. 854. ISBN 0-7167-4339-6. As a neurotransmitter Glycine is an inhibitory neurotransmitter in the central nervous system, especially in the spinal cord, brainstem, and retina. When glycine receptors are activated, chloride enters the neuron via ionotropic receptors, causing an Inhibitory postsynaptic potential (IPSP). Strychnine is a strong antagonist at ionotropic glycine receptors, whereas bicuculline is a weak one. Glycine is a required co-agonist along with glutamate for NMDA receptors. In contrast to the inhibitory role of glycine in the spinal cord, this behaviour is facilitated at the (NMDA) glutaminergic receptors which are excitatory. The LD50 of glycine is 7930 mg/kg in rats (oral), and it usually causes death by hyperexcitability. As A Potential Antipsychotic Dr. Daniel Javitt a clinical researcher had studied people who were addicted to PCP (angel dust) and Ketamine (special K) (Javitt, DC, Negative Schizophrenic Symptomatology and the Phencyclydine (PCP) Model of Schizophrenia, Hillside Journal of Psychiatry 1987 9:12-35. Their brains had been damaged by the use of this drug. In studies, it was found that their glutamate receptors had been damaged. Since use of PCP and ketamine creates psychosis similar to schizophrenia, it was hypothesized that giving glycine to people with schizophrenia would potentially reduce their psychotic symptoms. In a controlled study people with schizophrenia who were given glycine had their symptoms measurably reduced primarily in the area of negative and cognitive symptoms when used as an adjunct to current antipsychotics. There have been some psychiatrists who have used it out of study as a primary antipsychotic with benefits on positive as well as negative and cognitive symptoms. Glycine's primary drawback is its required use in powdered format. However, as an NMDA receptor modulator, it is part of a class of antipsychotics in study that do not cause tardive dyskinesia or diabetes, the current long term side effects of dopaminergic antipsychotics as well as not creating extra pyramdial side effects (movement disorders), weight gain or sedation. These medications along with other new classes of medications in study may eventually replace the current antipsychotics which, from Thorazine to Abilify, have all been based on the dopamine hypothesis and in depleting the levels of dopamine. They can create tardive dykinesia and other Parkinsonian movement disorders and potentially tardive psychosis which is still in study. Glycine, is part of a promising new class of treatment for schizophrenia that may promote a full recovery without debilitating physical side effects. See also *Glycine encephalopathy *Strychnine References Further reading * Dawson, R.M.C., Elliott, D.C., Elliott, W.H., and Jones, K.M., Data for Biochemical Research (3rd edition), pp. 1-31 (1986) ISBN 01-985-535-87 External links *GEO Specialty Chemicals, Inc. *Glycine *Computational Chemistry Wiki *Glycine cleavage system *Glycine, ChemSub Online * http://www.schizophrenia.com/glycinetreat.htm *http://www.sciencedaily.com/releases/2008/03/080326161658.htm category:Amino acids Category:Flavour enhancers Category:Glucogenic amino acids Category:Neurotransmitters Category:Proteinogenic amino acids